GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry 9, 137–150 (2022).
Ulrich-Lai, Y. M. & Herman, J. P. Neural regulation of endocrine and autonomic stress responses. Nat. Rev. Neurosci. 10, 397–409 (2009).
Cacioppo, J. T. et al. The neuroendocrinology of social isolation. Annu. Rev. Psychol. 66, 733–767 (2015).
O’Connor, D. B., Thayer, J. F. & Vedhara, K. Stress and health: a review of psychobiological processes. Annu. Rev. Psychol. 72, 663–688 (2021).
Devarbhavi, H. et al. Global burden of liver disease: 2023 update. J. Hepatol. 79, 516–537 (2023).
Russ, T. C. et al. Association between psychological distress and liver disease mortality: a meta-analysis of individual study participants. Gastroenterology 148, 958–966.e4 (2015).
Steel, J. L. et al. Depression, immunity, and survival in patients with hepatobiliary carcinoma. J. Clin. Oncol. 25, 2397–2405 (2007).
Wu, Y. et al. Psychological distress and eustress in cancer and cancer treatment: advances and perspectives. Sci. Adv. 8, eabq7982 (2022).
Antoni, M. H., Moreno, P. I. & Penedo, F. J. Stress management interventions to facilitate psychological and physiological adaptation and optimal health outcomes in cancer patients and survivors. Annu. Rev. Psychol. 74, 423–455 (2023).
Miller, B. M., Oderberg, I. M. & Goessling, W. Hepatic nervous system in development, regeneration, and disease. Hepatology 74, 3513–3522 (2021).
Jensen, K. J., Alpini, G. & Glaser, S. Hepatic nervous system and neurobiology of the liver. Compr. Physiol. 3, 655–665 (2013).
Adori, C. et al. Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging. Sci. Adv. 7, eabg5733 (2021).
Lee, J. A. et al. Disappearance of hepatic parenchymal nerves in human liver cirrhosis. Gut 33, 87–91 (1992).
Zsombok, A., Desmoulins, L. D. & Derbenev, A. V. Sympathetic circuits regulating hepatic glucose metabolism: where we stand. Physiol. Rev. 104, 85–101 (2024).
Puschel, G. P. Control of hepatocyte metabolism by sympathetic and parasympathetic hepatic nerves. Anat. Rec. A Discov. Mol. Cell Evol. Biol. 280, 854–867 (2004).
Kjaer, M. et al. No reinnervation of hepatic sympathetic nerves after liver transplantation in human subjects. J. Hepatol. 20, 97–100 (1994).
Laryea, M. et al. Metabolic syndrome in liver transplant recipients: prevalence and association with major vascular events. Liver Transpl. 13, 1109–1114 (2007).
Bogdanos, D. P., Gao, B. & Gershwin, M. E. Liver immunology. Compr. Physiol. 3, 567–598 (2013).
Li, X. et al. The immunological and metabolic landscape in primary and metastatic liver cancer. Nat. Rev. Cancer 21, 541–557 (2021).
Trefts, E., Gannon, M. & Wasserman, D. H. The liver. Curr. Biol. 27, R1147–R1151 (2017).
Sun, R. et al. Loss of SIRT5 promotes bile acid-induced immunosuppressive microenvironment and hepatocarcinogenesis. J. Hepatol. 77, 453–466 (2022).
Marszalek-Grabska, M. et al. Kynurenine emerges from the shadows—current knowledge on its fate and function. Pharmacol. Ther. 225, 107845 (2021).
Platten, M., Wick, W. & Van den Eynde, B. J. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res. 72, 5435–5440 (2012).
Trezeguet, V., Fatrouni, H. & Merched, A. J. Immuno-metabolic modulation of liver oncogenesis by the tryptophan metabolism. Cells 10, 3469 (2021).
Xu, B. et al. Metabolic rewiring of kynurenine pathway during hepatic ischemia–reperfusion injury exacerbates liver damage by impairing NAD homeostasis. Adv. Sci. 9, e2204697 (2022).
Antoniuk, S. et al. Chronic unpredictable mild stress for modeling depression in rodents: meta-analysis of model reliability. Neurosci. Biobehav. Rev. 99, 101–116 (2019).
Liu, K. et al. Metabolic stress drives sympathetic neuropathy within the liver. Cell Metab. 33, 666–675.e4 (2021).
Cervenka, I., Agudelo, L. Z. & Ruas, J. L. Kynurenines: tryptophan’s metabolites in exercise, inflammation, and mental health. Science 357, eaaf9794 (2017).
Liu, L. et al. Quantitative analysis of NAD synthesis–breakdown fluxes. Cell Metab. 27, 1067–1080.e5 (2018).
Wang, D. et al. Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage. Acta Pharm. Sin. B 11, 763–780 (2021).
Russell, G. & Lightman, S. The human stress response. Nat. Rev. Endocrinol. 15, 525–534 (2019).
Fries, G. R. et al. Molecular pathways of major depressive disorder converge on the synapse. Mol. Psychiatry 28, 284–297 (2023).
Anisman, H., Ravindran, A. V., Griffiths, J. & Merali, Z. Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Mol. Psychiatry 4, 182–188 (1999).
Philipp, M. & Hein, L. Adrenergic receptor knockout mice: distinct functions of 9 receptor subtypes. Pharmacol. Ther. 101, 65–74 (2004).
Tank, A. W. & Lee Wong, D. Peripheral and central effects of circulating catecholamines. Compr. Physiol. 5, 1–15 (2015).
London, E., Bloyd, M. & Stratakis, C. A. PKA functions in metabolism and resistance to obesity: lessons from mouse and human studies. J. Endocrinol. 246, R51–R64 (2020).
Zhang, H., Kong, Q., Wang, J., Jiang, Y. & Hua, H. Complex roles of cAMP-PKA-CREB signaling in cancer. Exp. Hematol. Oncol. 9, 32 (2020).
Xue, C. et al. Tryptophan metabolism in health and disease. Cell Metab. 35, 1304–1326 (2023).
Carambia, A. & Herkel, J. Dietary and metabolic modulators of hepatic immunity. Semin. Immunopathol. 40, 175–188 (2018).
Ma, C. et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science 360, eaan5931 (2018).
Tian, P. et al. Early life gut microbiota sustains liver-resident natural killer cells maturation via the butyrate–IL-18 axis. Nat. Commun. 14, 1710 (2023).
Hong, J. Y. et al. Long-term programming of CD8 T cell immunity by perinatal exposure to glucocorticoids. Cell 180, 847–861.e15 (2020).
Zhang, S. et al. Neuroendocrine regulation of stress-induced T cell dysfunction during lung cancer immunosurveillance via the kisspeptin/GPR54 signaling pathway. Adv. Sci. 9, e2104132 (2022).
Lelou, E. et al. The role of catecholamines in pathophysiological liver processes. Cells 11, 1021 (2022).
Du Preez, A. et al. Chronic stress followed by social isolation promotes depressive-like behaviour, alters microglial and astrocyte biology and reduces hippocampal neurogenesis in male mice. Brain Behav. Immun. 91, 24–47 (2021).
Leng, L. et al. Menin deficiency leads to depressive-like behaviors in mice by modulating astrocyte-mediated neuroinflammation. Neuron 100, 551–563.e7 (2018).
Wang, Y. et al. Inhibition of activated astrocyte ameliorates lipopolysaccharide-induced depressive-like behaviors. J. Affect. Disord. 242, 52–59 (2019).
Seehawer, M. et al. Necroptosis microenvironment directs lineage commitment in liver cancer. Nature 562, 69–75 (2018).
Ma, S. et al. Identification of a small-molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical mouse models. Sci. Transl. Med. 15, eadg6752 (2023).
Chen, C. et al. Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8+ T cell exhaustion and anti-PD-1 resistance. Cell Rep. Med. 5, 101686 (2024).
Liu, C. et al. Environmental eustress modulates beta-ARs/CCL2 axis to induce anti-tumor immunity and sensitize immunotherapy against liver cancer in mice. Nat. Commun. 12, 5725 (2021).
Luo, X. et al. SOX12 facilitates hepatocellular carcinoma progression and metastasis through promoting regulatory T-cells infiltration and immunosuppression. Adv. Sci. 11, e2310304 (2024).
Dapito, D. H. et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 21, 504–516 (2012).
Hu, H. et al. Long-term expansion of functional mouse and human hepatocytes as 3D organoids. Cell 175, 1591–1606.e19 (2018).
Ding, Y. et al. Intrinsic PD-L1 promotes antitumor activity of CD8+ cytotoxic T lymphocytes via in cis interaction with CD80. Cancer Commun. 42, 784–788 (2022).


















Leave a Reply